Placebos effect revealed in calmed brain cells

Detailed scans of brain cells in Parkinson's disease patients have revealed the action of the placebo effect on an unprecedented scale.

"It's the first time we've seen it at the single neuron level," says Fabrizio Benedetti, head of the team which conducted the experiments at the University of Turin Medical School in Italy.

When the patients in the study received a simple salt solution, their neurons responded in just the same way as when they had earlier received a drug which eased their symptoms.

"The research provides further evidence for a physiological underpinning for the placebo effect," says Jon Stoessl, at the University of British Columbia in Vancouver, Canada. His team demonstrated in 2001 that placebos can relieve symptoms by raising brain levels of dopamine, a beneficial neurotransmitter.

"We suggest that the changes we ourselves observed are also induced by release of dopamine," says Benedetti.

Abnormal firing

Parkinson's patients suffer from a lack of dopamine, meaning that brain cells in a region called the subthalamic nucleus firing in abnormal bursts. This triggers the familiar symptoms of muscle rigidity, tremors and slowness of movement.

Drugs which mimic dopamine, such as L-Dopa and apomorphine, can block abnormal firing. But now, Benedetti has shown that a simple saline solution did the same.

First, he "pre-conditioned" the patients by giving them three doses of apomorphine. Then he surgically implanted electrodes into each patient's subthalamic nucleus, each carrying sensors to monitor the firing activity of around 100 individual neurons.

During the surgery, for which the patients remained awake, he also administered the placebo. He found that it induced the same calming effect on neurons as the apomorphine.

Residual traces of apomorphine cannot explain the findings, he says: "Apomorphine effects only last for one hour, and the last apomorphine dose they received was 24 hours before the operation."

Cognitive vs conditioning

He suggest two possible explanations. The first is the "cognitive" hypothesis, where the physiological effects are triggered by the patient's expectation of benefits.

The second is the classic "conditioning" response. This was discovered in 1889 by the Russian psychologist, Ivan Pavlov, who found conditioning could induce dogs to salivate for food at the sound of a bell. "The context around the therapy could induce such a response," says Benedetti.

In his latest experiments, Benedetti is investigating whether the brain cells react to placebos in "naive" Parkinson's patients, who have not first been conditioned with genuine drugs.

"It's a logical next step," says Edzard Ernst, professor of complementary and alternative medicine at the University of Exeter, Devon, UK. He describes the new work as "one of the first glimpses of a mechanistic explanation for the placebo effect".

Journal reference: Nature Neuroscience: (DOI: 10.1038/nn1250)

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